Subunit composition of the human cytoplasmic dynein-2 complex.
Subunit composition of the human cytoplasmic dynein-2 complex.
复制标题
DOI：
10.1242/jcs.159038
复制
发表时间：
2014-11-01
影响因子：
4
通讯作者：
Stephens DJ
中科院分区：
文献类型：
--
作者：
Asante D;Stevenson NL;Stephens DJ
胞质动力蛋白-2是逆行鞭毛内运输（IFT）的马达，已知动力蛋白-2突变可引起骨骼肌纤毛病。在这里，我们首次定义了人细胞质动力蛋白-2复合物的组成。我们发现由纤毛病基因WDR34和WDR60编码的蛋白质是真正的动力蛋白-2中间链，并且都是动力蛋白-2功能所必需的。此外，我们发现TCTEX1D2是纤毛功能所必需的独特动力蛋白-2轻链。我们定义了dynein-1和dynein-2共有的几个亚基，包括tctex1（也称为DYNLT1）和tctex3（也称为DYNLT3），路障1（也称为DYNLRB1）和路障2（也称为DYNLRB2），以及LC8-1和LC8-2轻链（分别为DYNLL1和DYNLL2）。我们还发现NudCD3与动力蛋白-2结合，就像与动力蛋白-1结合一样。相比之下，常见的动力蛋白-1调节因子dynactin、LIS1（也称为PAFAH1B1）和BICD2未发现与动力蛋白-2相关。这些数据解释了为什么WDR34或WDR60突变会导致疾病，并确定了TCTEX1D2作为候选纤毛病基因。
Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. Here, we define for the first time the composition of the human cytoplasmic dynein-2 complex. We show that the proteins encoded by the ciliopathy genes WDR34 and WDR60 are bona fide dynein-2 intermediate chains and are both required for dynein-2 function. In addition, we identify TCTEX1D2 as a unique dynein-2 light chain that is itself required for cilia function. We define several subunits common to both dynein-1 and dynein-2, including TCTEX-1 (also known as DYNLT1) and TCTEX-3 (also known as DYNLT3), roadblock-1 (also known as DYNLRB1) and roadblock-2 (also known as DYNLRB2), and LC8-1 and LC8-2 light chains (DYNLL1 and DYNLL2, respectively). We also find that NudCD3 associates with dynein-2 as it does with dynein-1. By contrast, the common dynein-1 regulators dynactin, LIS1 (also known as PAFAH1B1) and BICD2 are not found in association with dynein-2. These data explain why mutations in either WDR34 or WDR60 cause disease, as well as identifying TCTEX1D2 as a candidate ciliopathy gene.
登录
查看更多内容
影响因子：
10.5
作者：
Mukhopadhyay, Saikat;Wen, Xiaohui;Jackson, Peter K.
通讯作者：
Jackson, Peter K.
DOI：
10.1126/science.1254198
发表时间：
2014-07-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McKenney RJ;Huynh W;Tanenbaum ME;Bhabha G;Vale RD
通讯作者：
Vale RD
影响因子：
6.6
作者：
Palmer, Krysten J.;MacCarthy-Morrogh, Lucy;Smyllie, Nicola;Stephens, David J.
通讯作者：
Stephens, David J.
影响因子：
4
作者：
Asante, David;MacCarthy-Morrogh, Lucy;Stephens, David J.
通讯作者：
Stephens, David J.
影响因子：
--
作者：
MITCHELL, DR;ROSENBAUM, JL
通讯作者：
ROSENBAUM, JL